The design of fully and partially substituted indole-functionalized cyclotriphosphazenes: Synthesis, chirality, thermal characterization, antioxidant, and in silico ADME-bioactivity profiling
JOURNAL OF MOLECULAR STRUCTURE, cilt.1381, 2027 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1381
- Basım Tarihi: 2027
- Doi Numarası: 10.1016/j.molstruc.2026.147815
- Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Ankara Üniversitesi Adresli: Evet
Özet
This study reports the synthesis and comprehensive characterization of partially and fully substituted hybrid inorganic/organic multiheterocyclic cyclotriphosphazenes bearing indol-3-yl pendant arms, alongside the evaluation of their thermal behavior, antioxidant potential and in silico ADME profiles. Initially, the reaction of indole-3-carboxaldehyde with N-methyl-1,2-diaminoethane yields the ligand N1-[(1H-indol-3-yl)methyl]-N2methyl-1,2-diaminoethane (L1). Subsequently, the equimolar reaction of L1 with hexachlorocyclotriphosphazene, N3P3Cl6 (HCCP), gave rise to the monospiro derivative (1). Reactions of 1 with nhexylamine, benzylamine, and 1-phenylpiperazine in stoichiometric ratios of 1:2 and 1:4 produce the corresponding geminal-bis (2a-2c) and tetrakis-amino (3a-3c) cyclotriphosphazenes. Geminal-phosphazenes (2a-2c) possess a chiral P-atom. Among these, the chirality of 2a and 2b was experimentally confirmed by circular dichroism (CD) analysis, alongside (R)-(-)-2,2,2-trifluoro-1-(9-anthryl)ethanol (CSA)-assisted 31P{1H} NMR spectroscopy for 2b. Whereas, the chiral assignment of 2c was made by inference from its structural configuration. Single-crystal X-ray diffraction confirms the geminal structure of derivative 2a. Intermolecular interactions were quantitatively determined via Hirshfeld surface (HS) analysis, revealing that H center dot center dot center dot H interactions dominate the crystal packing with a relative proportion of 68.3%. Structure-activity relationship (SAR) studies show that the DPPH center dot radical scavenging efficiency is primarily driven by the chemical nature and steric effects of the exocyclic substituents. Additionally, purely predictive in silico SwissADME and PASS-assisted bioactivity screenings were performed to assess theoretical pharmacokinetic limits and computational drug-likeness profiles. Their thermal behavior was monitored by thermogravimetric (TG) and differential thermogravimetric analyses (DTG). The calculated Limiting Oxygen Indexes (LOIs) (26.6-39.9) of these phosphazenes indicate that most are selfextinguishing materials.